CCK-1 and CCK-2 receptor agonism do not stimulate GLP-1 and neurotensin secretion in the isolated perfused rat small intestine or GLP-1 and PYY secretion in the rat colon

Abstract

Gastrin and cholecystokinin (CCK) are hormones released from endocrine cells in the antral stomach (gastrin), the duodenum, and the jejunum (CCK). Recent reports, based on secretion experiments in an enteroendocrine cell line (NCI-H716) and gastrin receptor expression in proglucagon-expressing cells from the rat colon, suggested that gastrin could be a regulator of glucagon-like peptide-1 (GLP-1) secretion. To investigate these findings, we studied the acute effects of CCK-8 (a CCK1/CCK2 (gastrin) receptor agonist) and gastrin-17 (a CCK2(gastrin) receptor agonist) in robust ex vivo models: the isolated perfused rat small intestine and the isolated perfused rat colon. Small intestines from Wistar rats (n = 6), were perfused intraarterially over 80 min. During the perfusion, CCK (1 nmol/L) and gastrin (1 nmol/L) were infused over 10-min periods separated by washout/baseline periods. Colons from Wistar rats (n = 6) were perfused intraarterially over 100 min. During the perfusion, CCK (1 nmol/L), vasoactive intestinal peptide (VIP) (10 nmol/L), and glucose-dependent insulinotropic polypeptide (GIP) (1 nmol/L) were infused over 10-min periods separated by washout/baseline periods. In the perfused rat small intestines neither CCK nor gastrin stimulated the release of GLP-1 or neurotensin. In the perfused rat colon, neither CCK or VIP stimulated GLP-1 or peptide YY (PYY) release, but GIP stimulated both GLP-1 and PYY release. In both sets of experiments, bombesin, a gastrin-releasing peptide analog, served as a positive control. Our findings do not support the suggestion that gastrin or CCK participate in the acute regulation of intestinal GLP-1 secretion, but that GIP may play a role in the regulation of hormone secretion from the colon.

Keywords: CCK; GIP; GLP-1; PYY; VIP; bombesin; cholecystokinin; colon; ex vivo; gastrin; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; hormones; isolated perfused colon; isolated perfused small intestine; neurotensin; peptide YY; rat; secretion; vasoactive intestinal peptide.

Figure 1

Neurotensin (a) and Glucagon‐like peptide‐1 (GLP‐1) (c) output (fmol/min) in the venous effluent from the isolated perfused rat small intestine (Wistar, n = 6). After a 10‐min baseline, cholecystokinin (CCK) was infused intraarterially (1 nmol/L, 10 min). After a 20‐min washout, gastrin was infused intraarterially (1 nmol/L, 10 min). Finally, bombesin (BBS, a gastrin‐releasing peptide analog) was infused over 5 min as a positive control. Hormone outputs) for neurotensin (b) and GLP‐1 (D). Filled circles represent areas hormone output over 10 min for individual rats, (5 min periods for BBS). Data are means with standard errors of the mean. Post hoc comparisons were made by one‐way analyses of variance (ANOVA) with Bonferroni corrections

Figure 2

Glucagon‐like peptide‐1 (GLP‐1) (a) and peptide YY (PYY) (c) output (fmol/min) in the venous effluent from the isolated perfused rat colon (Wistar, n = 6). After a 10‐min baseline, Cholecystokinin (CCK) was infused intraarterially (1 nmol/L, 10 min). After a 15‐min washout, vasoactive intestinal peptide (VIP) was infused intraarterially (10 nmol/L, 10 min), after a 15‐min washout glucose‐dependent insulinotropic polypeptide (GIP) was infused intraarterially (1 nmol/L, 10 min). Finally, Bombesin (BBS, a gastrin‐releasing peptide analog) was infused over 5 min as a positive control. Hormone outputs for GLP‐1 (b) and PYY‐1 (d). Filled circles hormone outputs over 10‐min periods for individual rats, (5‐min periods for BBS). Data are means with standard errors of the mean. Post hoc comparisons were made by one‐way analyses of variance (ANOVA) with Bonferroni corrections